The development of a non-invasive technique of measuring both bronchial and alveolar epithelial permeability is proposed which will serve as an early indicator of lung injury after pollutant exposure. It involves the measurement of changes in the protective barrier function of the airway mucosa. The proposed investigations have two goals: First, the establishment of a method for measuring lung permeability in the same animal repeatedly, second, to investigate the effect of O3 and NO2 on lung permeability. The method consists of the inhalation of labelled solutes of certain molecular sizes - like 99mTc-DTPA - and the subsequent measurement of their clearance by external counting of the lung activity. Appearance of the solute in the blood will be monitored at the same time in order to correct for its contribution to the lung counts. Two animal species will be involved, rats and dogs. In the dogs, gamma-camera imaging will be used which allows determination of regional clearance rates. For differentiating between bronchial and alveolar permeability, two differently sized aerosols of the tracers will be applied: integral 2 Mum and integral 8 Mum mass median aerodynamic diameter. After establishment of the method, the animals will be exposed to varying concentrations of O3 and NO2 down to relevant urban concentrations, e.g., less than or equal to 8 0.1 ppm . Acute and chronic intermittent exposures as well as cycles including weeks of exposure alternating with weeks free of exposure are planned. This will give some information about adaptation processes of oxidant induced alterations of lung permeability. Since the same animal will be followed up and measured repeatedly, it will serve as its own control. In order to get a clearer understanding about the underlying mechanism of oberved permeability changes, several dogs exposed to selected O3 and NO2 concentrations will be prepared for measuring lung lymph flow. In these dogs, measurement of lymphatic clearance of i.v. administered or inhaled solutes will distinguish between endothelial and/or epithelial permeability changes after pollutant exposure.